Erysipelothrix infection

INTRODUCTION — Erysipelothrix rhusiopathiae is a pleomorphic, non-spore forming, gram-positive bacillus capable of causing self-limited soft tissue infection or serious systemic infection. E. rhusiopathiae is widespread in nature around the world and also infects domestic and marine animals; it is found in sheep, horses, cattle, chickens, turkeys, crabs, fish, dogs, and cats [1]. The risk may be highest from swine exposure because of the large number of exposed farmers.

Infection in humans is usually due to occupational exposure. Thus, slaughterhouse workers, butchers, fishermen, aquarium workers, farmers, and veterinarians are at risk for infection with E. rhusiopathiae [2-5].

PATHOGENESIS — Little is known about the pathogenesis of human E. rhusiopathiae infection. The following observations have been made in vitro and in animal studies:

●E. rhusiopathiae is a virulent organism with a capsule that resists phagocytosis and may contribute to intracellular survival (in the absence of opsonization with specific antibody) [6,7].

●Intracellular survival of virulent organisms in macrophages is associated with reduced stimulation of the oxidative respiratory burst [7].

●The SpaA protein is a surface antigen of E. rhusiopathiae. It acts as an adhesion protein for the attachment of E. rhusiopathiae to host cells [8]. The pathogenic significance of this protein was suggested in a mouse model in which exposure to SpaA antigen was protective in a vaccination system [9].

●The enzymes neuraminidase and hyaluronidase may contribute to the pathogenicity of Erysipelothrix [10].

●Other virulence factors include cell wall–associated proteins such as transporter and adhesion proteins [11].

CLINICAL MANIFESTATIONS — The clinical spectrum of human infection includes three major forms of disease:

●Localized cutaneous (erysipeloid) infection

●Diffuse cutaneous infection

●Systemic infection (bacteremia with or without endocarditis)

Localized cutaneous infection — The most common form of human infection due to E. rhusiopathiae is the localized cutaneous form, known as erysipeloid of Rosenbach [12]. When localized infection occurs, it is a usually subacute cellulitis and involves the fingers and/or hands (the sites of exposure). Abrasions or wounds of the skin serve as the portal of entry of the organism. As an example, erysipeloid has been described on the fingers or hands of fisherman or seafood packers who suffer minor trauma while handling contaminated shrimp, crab, or fish [13,14]. Infection can also occur following cat or dog bites. In a review from 18 emergency departments in the United States, E. rhusiopathiae was isolated from 2 of 57 patients with infected cat bites [15].

The incubation period following inoculation may last two to seven days. Symptoms begin with pain at the site of inoculation (described as throbbing, itching, burning, or tingling). The skin lesion typically progresses slowly from a small red macule at the inoculation site to a well-developed violaceous lesion with central clearing and a raised border. Swelling is typically minimal; patients typically complain of stiffness and pain in the involved fingers. Local lymphangitis and adenitis occur in approximately 30 percent of cases. Systemic symptoms such as high fever or chills are uncommon (about 10 percent of patients) [16].

Diffuse cutaneous infection — Diffuse cutaneous disease is characterized by proximal progression of involvement from the inoculation site and/or involvement of additional sites; such cases are rare [12]. Lesions may be urticarial or bullous, and these patients frequently have fever and arthralgia. Blood cultures are usually negative [12].

Most patients with diffuse cutaneous infection have the same types of exposures as those with localized cutaneous infection. However, eating contaminated seafood or undercooked pork has been associated with diffuse cutaneous disease. In such cases, it is presumed that bacteremia precedes the appearance of diffuse cutaneous disease.

Systemic infection — Systemic infection with bacteremia is relatively uncommon. Most patients present with fever. Approximately 40 percent of patients with systemic infection have antecedent or concurrent skin lesions suggestive of erysipeloid [3]. Cutaneous serpiginous lesions or multiple bullous lesions on the trunk and extremities may be seen. Patients with severe underlying liver or heart disease and systemic infection due to Erysipelothrix infection may have a clinical presentation resembling gram-negative sepsis [17].

The epidemiologic exposures in patients with systemic infection are the same as those for localized cutaneous infection; persistent bacteremia has been reported after the ingestion of contaminated meat. Chronic liver disease is an important predisposing factor; more than one-third of patients with systemic infection are people with an alcohol use disorder [3,12,18]. Bacteremia may also be seen in other immunocompromised patients, especially those receiving corticosteroid and/or cytotoxic drug therapy [17,19,20].

Endocarditis — E. rhusiopathiae bacteremia is often complicated by endocarditis; in one report, 90 percent of 49 cases of serious infection had proven or presumed endocarditis [3]. However, this figure may be a falsely elevated rate due to reporting bias in case reports, since a number of cases with bacteremia in the absence of endocarditis have also been reported [17,19-23].

Nearly all reported cases of endocarditis have involved native heart valves, with propensity for involvement of the aortic valve [3,24-30]. Erysipelothrix endocarditis frequently causes extensive valve destruction. In one series, one-third of patients died and an additional one-third required valve replacement [3].

Complications of Erysipelothrix endocarditis may include congestive heart failure, valve perforation, myocardial abscess, cerebral infarctions, and acute renal failure due to proliferative glomerulonephritis [31].

Other manifestations — Uncommon forms of infection due to E. rhusiopathiae include brain abscess, meningitis, endophthalmitis, intra-abdominal abscess, psoas abscess, osteomyelitis (including vertebral osteomyelitis), spondylodiscitis, septic arthritis, prosthetic joint infection, tenosynovitis, epidural and paravertebral abscesses, pneumonia, necrotizing fasciitis, and peritoneal dialysis-related peritonitis with bacteremia [19,32-47].

DIAGNOSIS — A provisional diagnosis can often be made based on a history of appropriate epidemiologic exposure together with the characteristic physical findings. Erysipelothrix infection might be suspected in cutaneous or systemic gram-positive infections that fail to respond to vancomycin. Gram stain and culture of aspirated material are often negative because the organism is deep within the dermis.

Organisms may be isolated from the blood with routine commercial blood culture media; growth is usually recognized in two to three days. However, errors in identification can occur; the organism has been misidentified as Lactobacillus or Enterococcus species [48]. Commercial systems such as Vitek2 and the API system identify E. rhusiopathiae reliably. E. rhusiopathiae has been identified by 16SrRNA-based gene sequencing from culture-negative, surgically excised heart valves [49]. Matrix-assisted laser desorption/ionization–time of flight mass spectroscopy (MALDI-TOF MS) accurately and rapidly identifies Erysipelothrix [30,50].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of localized cutaneous infection (erysipeloid) includes streptococcal or staphylococcal cellulitis. The diagnosis of erysipeloid is favored by a history of occupational exposure, lesions on the fingers, a subacute course, violaceous hue (as opposed to erythema), absence of suppuration, absence of pitting edema, and pain out of proportion with physical findings.

TREATMENT — Erysipeloid skin lesions may resolve in the absence of specific therapy; spontaneous resolution typically occurs within three weeks [51]. However, appropriate antibiotic therapy shortens the clinical illness and reduces the risk of relapse [24]. Local heat may be helpful for patients with arthritis and painful, swollen lesions. Surgical incision or debridement of localized lesions is not indicated.

Antibiotic susceptibility — Penicillin is the drug of choice for all forms of Erysipelothrix infection based on in vitro data; there are no comparative clinical trials (table 1) [2-5,17,18,20,21,24,51-53]. Amoxicillin may be used as first-line therapy for localized skin infection [54]. In vitro, penicillin and imipenem are the most active agents; other active agents include other beta-lactam antibiotics such as cephalosporins, fluoroquinolones, clindamycin, daptomycin, and linezolid [55,56]. Penicillin resistance has been described [57].

Agents that are not consistently active against Erysipelothrix include macrolides, tetracyclines, and chloramphenicol; these should not be used in the treatment of disseminated infection. E. rhusiopathiae is typically resistant to sulfonamides, trimethoprim-sulfamethoxazole, vancomycin, and aminoglycosides [3,52,53]. Intrinsic resistance to vancomycin is a clinically relevant characteristic, since this antibiotic is often used empirically in treatment of gram-positive infections. However, limited data suggest that Erysipelothrix is susceptible to daptomycin [55]. Bacteremia caused by penicillin-resistant Erysipelothrix has been described; the patient was successfully treated with ceftriaxone [57]. Resistance to cefazolin has been described [58].

Clinical approach — The approach to antibiotic therapy depends on the clinical manifestations and results of blood cultures (table 1).

For localized cutaneous infection, oral therapy with penicillin V (500 mg every 6 hours) or amoxicillin (500 mg every 8 hours) should be administered; cephalexin (500 mg every 6 hours) is an acceptable regimen in the absence of immediate hypersensitivity to penicillin. In the setting of penicillin allergy, ciprofloxacin (250 mg every 12 hours) or clindamycin (300 mg every 8 hours) may be administered. Seven days of therapy is usually curative based on case reports and case series; the 2014 Infectious Diseases Society of America (IDSA) guidelines recommend 7 to 10 days of treatment for erysipeloid [54]. Five days of therapy may also be sufficient based on current therapy for other forms of cellulitis if there is a clinical response.

For diffuse cutaneous disease or systemic infection, parenteral therapy should be administered with penicillin G (2 to 4 million units every 4 hours). Alternative therapies include ceftriaxone (2 g once daily), imipenem (500 mg every 6 hours), or a fluoroquinolone (ciprofloxacin 400 mg every 12 hours or levofloxacin 500 mg once daily) or daptomycin (6 mg/kg intravenously once daily) [55]. The treatment duration should be guided by the clinical response and the underlying health of the patient. Many patients with diffuse cutaneous disease can be switched to oral therapy after clinical response occurs. Short courses of antibiotic therapy (eg, 5 to 10 days) are often curative in such patients; the 2014 IDSA guidelines recommend 7 to 10 days of treatment [54]. For patients with bacteremia in the absence of endocarditis or signs of metastatic infection, some experts favor a minimum of four weeks of therapy [3,24]. Two weeks of intravenous therapy followed by two to four weeks of oral therapy has also been successful [24].

SUMMARY AND RECOMMENDATIONS

●Erysipelothrix rhusiopathiae is a gram-positive bacillus capable of causing self-limited soft tissue infection or serious systemic infection in humans. It is widespread in nature and infects domestic animals. Infection in humans is usually due to occupational exposure. Slaughterhouse workers, butchers, fishermen, farmers, and veterinarians are at risk for infection with E. rhusiopathiae. (See 'Introduction' above.)

●There are three major forms of disease: localized cutaneous (erysipeloid) infection, diffuse cutaneous infection, and systemic infection (bacteremia with or without endocarditis). (See 'Clinical manifestations' above.)

●Localized cutaneous infection is a subacute cellulitis that usually involves the fingers and/or hands; abrasions or wounds of the skin serve as the portal of entry of the organism. Following an incubation period of two to seven days, symptoms begin with pain at the site of inoculation. The skin lesion typically progresses from a small red macule at the inoculation site to a well-developed violaceous lesion with central clearing and a raised border. (See 'Localized cutaneous infection' above.)

●Diffuse cutaneous disease is characterized by proximal progression of involvement from the inoculation site and/or involvement of additional sites. Lesions may be urticarial or bullous, and these patients frequently have fever and arthralgia. (See 'Diffuse cutaneous infection' above.)

●Systemic infection with bacteremia (with or without endocarditis) presents with fever; approximately 40 percent of patients with systemic infection also have antecedent or concurrent skin lesions suggestive of erysipeloid. E. rhusiopathiae bacteremia is often complicated by endocarditis. (See 'Systemic infection' above.)

●A provisional diagnosis can be made based on a history of appropriate epidemiologic exposure together with the characteristic physical findings. Organisms may be isolated from the blood with routine commercial blood culture media; growth is usually recognized in two to three days. (See 'Diagnosis' above.)

●For treatment of localized cutaneous infection, we suggest oral therapy with penicillin V or amoxicillin (Grade 2C). In the setting of penicillin allergy, cephalexin (in the absence of immediate hypersensitivity to penicillin), ciprofloxacin or clindamycin are acceptable alternatives. Treatment duration is five to seven days; dosing is outlined in the table (table 1). (See 'Clinical approach' above.)

●For treatment of diffuse cutaneous disease, we suggest parenteral therapy with penicillin G (Grade 2C). Alternative therapies include ceftriaxone, imipenem, a fluoroquinolone, or daptomycin (table 1). (See 'Clinical approach' above.)

●For treatment of systemic infection with bacteremia (with or without endocarditis), we suggest parenteral therapy with penicillin G (Grade 2C). Alternative therapies include ceftriaxone, cefazolin, imipenem, a fluoroquinolone, or daptomycin. Treatment duration is at least four weeks; dosing is outlined in the Table (table 1). (See 'Clinical approach' above.)